Chau Dang

Change in serum and skin histology eosinophils in the total cohort. *, P < 0.05.

Purpose:Eosinophil-related cutaneous adverse events (ercAE) are common after systemic cancer therapies and often affect health-related quality of life (HRQoL). In this study, we investigate the efficacy and safety of benralizumab for ercAE following systemic cancer therapies. Patients and Methods:This single-arm, single-center, open-label, phase II trial (NCT04552288) in patients with cancer and systemic therapy-associated ercAE was performed from September 2020 to October 2023. Benralizumab 30 mg was administered subcutaneously according to the approved dosing schedule, with 3 doses given every 4 weeks followed by 3 doses given every 8 weeks. The primary endpoint was clinical response (reduction in ercAE to Common Terminology Criteria for Adverse Events grade ≤ 1 by week 4). Secondary endpoints included HRQoL, rash body surface area (rash-BSA), eosinophil levels, and AE. Results:At baseline (N = 47), ercAE were attributed to phosphoinositide 3-kinase inhibitors in 47%, checkpoint inhibitors in 21%, tyrosine kinase inhibitors in 9%, and antibody–drug conjugates in 9%; ercAE were grade 2 and 3 in 49% and 51% of patients, respectively. Of the 42 patients evaluable for the primary endpoint, 76% of patients (n = 32/42) responded to treatment by week 4; median ercAE grade decreased from 2 to 1 (P < 0.0001). Patients exhibited improved HRQoL, reduced mean rash-BSA, and decreased peripheral eosinophils. All patients with ercAE following alpelisib (n = 18) or enfortumab vedotin (n = 4) responded by week 4 (both P < 0.05). Most AE were mild to moderate and likely unrelated to benralizumab. Conclusions:Benralizumab demonstrated favorable efficacy and safety against grade 2/3 ercAE related to novel cancer therapies. Further investigation in larger placebo-controlled trials is warranted.

Clinical response to benralizumaba in the total cohort and by culprit agent. Change in BSA and HRQoL from baseline to week 4. aResponse was defined as a reduction in ercAE to grade ≤ 1 by week 4. PI3Ki, PI3K inhibitor. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Figure 1 from Benralizumab for Eosinophil-Related Cutaneous Adverse Events of Anticancer Therapy: A Phase II Trial

Table 1 from Benralizumab for Eosinophil-Related Cutaneous Adverse Events of Anticancer Therapy: A Phase II Trial

Change in biomarkers from baseline to week 4 in the total cohort. IFN, interferon; TNF, tumor necrosis factor. *, P < 0.05.

Table 2 from Benralizumab for Eosinophil-Related Cutaneous Adverse Events of Anticancer Therapy: A Phase II Trial

Purpose: Eosinophil-related cutaneous adverse events (ercAE) are common after systemic cancer therapies and often affect health-related quality of life (HRQoL). In this study, we investigate the efficacy and safety of benralizumab for ercAE following systemic cancer therapies. Patients and Methods: This single-arm, single-center, open-label, phase II trial (NCT04552288) in patients with cancer and systemic therapy-associated ercAE was performed from September 2020 to October 2023. Benralizumab 30 mg was administered subcutaneously according to the approved dosing schedule, with 3 doses given every 4 weeks followed by 3 doses given every 8 weeks. The primary endpoint was clinical response (reduction in ercAE to Common Terminology Criteria for Adverse Events grade ≤ 1 by week 4). Secondary endpoints included HRQoL, rash body surface area (rash-BSA), eosinophil levels, and AE. Results: At baseline (N = 47), ercAE were attributed to phosphoinositide 3-kinase inhibitors in 47%, checkpoint inhibitors in 21%, tyrosine kinase inhibitors in 9%, and antibody–drug conjugates in 9%; ercAE were grade 2 and 3 in 49% and 51% of patients, respectively. Of the 42 patients evaluable for the primary endpoint, 76% of patients (n = 32/42) responded to treatment by week 4; median ercAE grade decreased from 2 to 1 (P < 0.0001). Patients exhibited improved HRQoL, reduced mean rash-BSA, and decreased peripheral eosinophils. All patients with ercAE following alpelisib (n = 18) or enfortumab vedotin (n = 4) responded by week 4 (both P < 0.05). Most AE were mild to moderate and likely unrelated to benralizumab. Conclusions: Benralizumab demonstrated favorable efficacy and safety against grade 2/3 ercAE related to novel cancer therapies. Further investigation in larger placebo-controlled trials is warranted.

Supplemental table 1-Covariates analyses; Supplemental Table 2-Genotype frequency, variant allele frequency and Hardy-Weinberg Equilibrium (HWE) of variants in CYPs